Plasminogen Activator (PA) from pig heart has been purified to 100,000-200,000 CTA U/mg. It has immunologic identity with activator isolated from pig lung and kidney as well as the circulating activator in pig plasma, but no identity with the activator isolated from the supernatant of pig kidney cell cultures. Another difference between tissue-derived and cell culture-derived PA is that tissue-derived activator is unable to rapidly activate purified plasminogen, an observation shared with other investigators. However, we have isolated a fraction of pig heart that accelerates the activity of pig heart PA on plasminogen. In this coming year we will attempt to further purify the accessory factor. Our current hypothesis is that tissue-derived PA is in an inactive form, and that accessory factor is responsible for activation of PA by unfolding of the PA molecule on the accessory factor surface or by some other mechanism. We will study the acceleration mechanism to determine if activation of PA is achieved. The effects of ions and various inhibitors on PA action also will be undertaken. Purification of human tissue activator will continue with the primary objective to produce an antiserum against human tissue plasminogen activator. This would allow development of an immunochemical assay for circulating blood activator in man.